Table 2.
Overview of the efficacy of select novel therapies in Mature B-Cell neoplasms: indolent histology.
| Authors | Drug | Target | Phase | Setting | N° of pts | ORR% (CR %) | PFS% (y) | PFS median (mo.s) | *AEs | |
|---|---|---|---|---|---|---|---|---|---|---|
| CLL/SLL | Byrd et al. (121) | Acalabrutinib | BTK | I | R/R with 17p alteration | 61 | 95% | NR | 14.3 | Dyarrhea |
| CLL/SLL | Byrd et al. (121) | Ublintuximab | CD20 | II | Naïve. Two arms of 1 g/day and 2 g/day | 80 | 67% | NR | 20.3 | 12% neutropenia in 2 g/day arm |
| CLL/SLL | Nastoupil et al. (230) | Ublintuximab | CD20 | I | Dose escalation. Post-Rituximab. In combination with umbralisib, and ibrutinib | 46 | 84% | NR | NR | 24% |
| CLL/SLL/ | Ding et al. (83) | Pembrolizumab | PD-1 | II | R/R carrying 17p alteration and IGHV unmutated | 16 | 44% | NR | NR | ND |
| CLL/SLL | Gopal et al. (139) | Idelalisib | PI3K | II | R/R. In combination to Brivatinib | 125 | 57% (6%) | 12% (2 y) | 11 | ND |
| CLL/SLL | Liu et al. (147) | Entospletinib | Syk | II | R/R. dosing 1,6 g/daily | 41 | 61% | NR | 13.8 | ND |
| CLL/SLL | Seymour et al. (210) | Venetoclax | BCL2 | II | R/R. 17p deletion In combination to Rituximab | 49 | 86% | 82% (2 y) | NR | 67% |
| CLL/SLL | Jaglosky et al. (119) | Ibrutinib | BTK | 1b/II | R/R with 17p deletion. Dosing 420mg/day. In combination to Ofatumumab | 71 | 83% (1.5%) | 83% (1 y) | NR | 11% led discontinuation |
| CLL/SLL | Rosenthal et al. (18) | Ibrutinib | BTK | III | R/R. In combination to Bendamustine and Rituximab | ND | 93% 40% | 96% (1 y) | NR | ND |
| FL | Younes et al. (231) | Nivolumab | PD1 | I | R/R in combination to ibrutinib | 40 | 36% | NR | 5 | 13% anemia |
| FL | Ganjo et al. (232) | Ocaratuzumab | CD20 FcγRIIIa | I/II | R/R with low affinity genotype FcγRIIIa | 50 | 30% | NR | 9.2 | ND |
| FL | Czuczuman et al. (233) | Ofatumumab | CD20 | I/II | R/R. Dosing 500 mg/day | 27 | 22% | NR | 5.8 | Neutropenia |
| FL | Westin et al. (234) | Pidilizumab | PD1 | II. | R/R. Dosing 3 mg/kg IV every 4 weeks. In combination to Rituximab | 32 | 52% | NR | 15.4 | No AEs grade >2 |
| FL | Westin et al. (234) | Pidilizumab | PD-1 | II | R/R combined with Rituximab | 29 | 66% | NR | 18.8 | No AEs grade >2 |
| FL | Gopal et al. (141) | Idelalisib | PI3Kd | II | R/R. Dosing 150mg twice daily | 125 | 57% (50%) | NR | 11 | Neutropenia 27% |
| FL | Bartlett et al. (235) | Ibrutinib | BTK | I | Naïve in combination with Rituximab. Dosing 560mg/day | 31 | 37.5% 12.5% | 80.4% (2y) | 14 | Neutropenia 10% |
| FL | Davids et al. (236) | Venetoclax | BCL2 | I | R/R to Bendamustine Rituximab. Dosing 1.2 g/day | 29 | 38% | NR | 11 | Neutropenia 11% |
| MZL | Noy et al. (237) | Ibrutinib | BTK | II | R/R. dosage 560 mg/day | 63 | 48% | NR | 14.2 | pneumonia 8% |
| B-NHLnos | Goebler et al. (109) | Blinatumumab | CD3/CD19 | I | R/R maximum dose tolerated | 35 | 69% | NR | 13,5 | ND |
| B-NHLnos | Ansell et al. (238) | Ipilimumab | CTLA-4 | I | R/R. 3 mg/kg/mo.s × 4mo.s | 18 | 11% | NR | 16 | ND |
| iNHL | Cheson et al. (45) | Obintuzumab | CD20 | III | Randomly comparing to bendamustine in R/R to rituximab | 396 | NR | NR | 22.5 | ND |
*
Grade ≥3 non hematological AEs, only.
ASCT, Autologous Stem Cell Transplantation; B-NHL, B-NHL not otherwise specified; CLL/SLL, Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia; DLBCL, Diffuse Large B cell Lymphoma; FL, Follicular Lymphoma; HG-BCL, High Grade B-cell lymphoma; IGHV, Immunoglobulin G Heavy Variable chain; iNHL, indolent NHL; IV, intravenous; LBCL Large B-cell lymphoma; MCL, Mantle Cell Lymphoma; mo.s, months; MZL, Marginal Zone Lymphoma;; ND, Not Documented NR, Not Reached; pts, patients; R/R, Refractory/relapsed; y, years.